Circulating Asymmetric Dimethylarginine in Adults with Essential Hypertension Compared with Normotensive Controls: A Systematic Review and Meta-Analysis

Abstract

Background: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor and a candidate mediator of the endothelial dysfunction accompanying raised arterial pressure. Prior meta-analyses covered coronary disease, heart failure, chronic kidney disease and preeclampsia, but none quantified the essential hypertension versus normotension contrast.

Objective: To quantify the difference in circulating ADMA between adults with essential hypertension and normotensive controls, and to characterise its clinical and methodological moderators.

Methods: MEDLINE and Europe PMC were searched for studies of circulating ADMA in essential hypertension with a concurrent normotensive group. Effect sizes for paywalled reports publishing only a direction and p-value were recovered from test statistics and group sizes, graded into three tiers, with non-significant results entered as zero. Hedges g was pooled under a random-effects model (REML, Knapp–Hartung); bias was appraised with the Newcastle–Ottawa Scale.

Results: Twenty-four studies contributed 2,201 participants (1,293 hypertensive, 908 normotensive). ADMA was higher in essential hypertension, Hedges g = 0.642 (95% CI 0.340 to 0.945; p = 0.0002), with I² = 81.4% and a 95% prediction interval (−0.673 to 1.957) including zero. Directly readable studies gave g = 0.972 and recovered studies g = 0.330 (interaction p = 0.019). Small-study effects were present (Begg p = 0.029; trim-and-fill g = 0.407), yet the estimate stayed positive across all 39 sensitivity specifications.

Conclusion: The plausible effect is about 0.33 to 0.64 standardised units, roughly 0.1 micromoles per litre. Certainty is very low and the distributions overlap too much for ADMA to discriminate between individuals.